Ischemic Preconditioning Improves Islet Recovery After Pancreas Cold Preservation

Increasing evidence supports the beneficial effects of ischemic preconditioning (IPC) of organs on subsequent ischemia. The aim of this study was to assess the effects of IPC of the pancreas on islet cell recovery after cold preservation using a rat model. The pancreas was deprived of perfusion (celiac artery and superior mesenteric artery occlusion) for 10 minutes followed by 10 minutes of reperfusion. Islet isolation was performed after 18 hours of cold ischemia. Glands undergoing IPC yielded significantly greater numbers of islets than controls. Following overnight culture, a significantly greater proportion of islets was recovered from IPC-treated pancreata. Microarray genomic analysis of pancreatic tissue revealed a significant differential expression of ∼600 unique mRNA strands within IPC pancreata compared to only <100 unique mRNA strands within non-IPC pancreata (>2-fold change; P < .05). Proteomic analysis revealed significant differential expression of at least 5 proteins >1.5-fold change; P < .05) within the IPC vs control group. Our data indicated that IPC of the pancreas prior to cold preservation was associated with improved islet cell recovery after cold ischemia. IPC of the pancreas may represent a viable therapeutic intervention to increase islet transplantation success from a single donor and to maximize organ utilization.     

Pretreatment With Calcitonin Gene-Related Peptide Attenuates Hepatic Ischemia/Reperfusion Injury in Rats

Objective

Oxygen free radicals and apoptosis play important roles in liver ischemia/reperfusion (I/R) injury. We sought to investigate the protective effect of calcitonin gene-related peptide (CGRP) to attenuate liver I/R injury due to oxygen free radicals and apoptosis.

Materials and Methods

Harvested rat livers were perfused via the portal vein with 60 mL of 4°C histidine-tryptophan-ketoglutarate (HTK) solution alone in the control group, or with the same solution containing CGRP (3 μg/10 g body weight) in the experimental group. After 24 hours of cold storage, hepatic enzyme leakage, portal venous pressure, oxygen consumption, total adenine nucleotides (TAN), bile production, lipoperoxide (LPO) release, apoptosis, and histochemical changes were evaluated upon 45 minutes of isolated reperfusion.

Results

Compared with control livers, CGRP-treated organs showed significantly decreased alanine aminotransferase (ALT) and glutamate-lactate dehydrogenase (GLDH) leakage and portal venous pressure (2.0 ± 0.3 vs 4.0 ± 0.4 mm Hg; P < .01), with significantly increased bile production (8.56 ± 0.76 vs 3.34 ± 0.68 μL/g/45 min; P < .01), oxygen consumption (5.14 ± 0.4 vs 2.57 ± 0.2 μL/g/min; P < .01), and total adenine nucleotides (TAN) (11.1 ± 0.71 vs 7.02 ± 0.53 μmol/g; P < .01) upon reperfusion as signs of recovered viability. We observed infrequent positive terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining, especially in sinusoidal lining cells (SLC). The percentage of TUNEL-positive cells in the CGRP group was significantly decreased compared with the control group: (4.1 ± 0.67 vs 8.0 ± 1.27; P < .05). Perfusate levels of low molecular weight (LMW) histone-associated DNA fragments (0.36 ± 0.04 vs 0.53 ± 0.06 AU; P < .05) were also decreased, coupled with strong 5′-nucleotidase (5′-NT) and LDH activity staining concentrated on the endothelial cells. LPO release in the perfusate was largely decreased: (0.12 ± 0.02 vs 0.36 ± 0.04 nmoL/g, P < .01).

Conclusion

CGRP ameliorated liver I/R injury due to reactive oxygen species and apoptosis.     

Persufflation Improves Pancreas Preservation When Compared With the Two-Layer Method

Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the large dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in low islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from donors after cardiac death and preserved by either TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from several regions of the pancreas were sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries and significantly less autolysis/cell death relative to regions not exposed to persufflation or to tissues preserved with TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.     

体外循环心脏手术期间降钙素基因相关肽的变化

为探讨体外循环（ＣＰＢ）心脏手术病人降钙素基因相关肽（ＣＧＲＰ）的变化和临床意义，对１５例先天性心脏病和１１例风湿性心脏病（男１９例，女７例；年龄６～５６岁；体重１３～６８ｋｇ）行ＣＰＢ心脏手术的病人，采血用放免法测定ＣＧＲＰ含量。结果麻醉后转流前、阻断主动脉２０、４０分钟、开放主动脉即刻、开放后２０、４０分钟、术后６小时和术后１０天共８个时点ＣＧＲＰ含量分别为２．３９２±１．３７５、７．４８２±６．７９３、４．６６６±２．７１２、６．５４０±４．５００、７．８２６±７．２６９、９．２８９±４．９７６、５．２４２±４．０１４、３．９８３±２．８８７ｐｍｏｌ／Ｌ。与转流前比较，ＣＧＲＰ含量在阻断主动脉至开放主动脉明显升高，开放主动脉４０分钟达高峰（Ｐ＜０．００１），术后６小时稍有回落，但仍高于转流前（Ｐ＜０．００５），术后１０天虽显著回落，但仍显著高于转流前水平（Ｐ＜０．０５）。结论：ＣＰＢ期间ＣＧＲＰ升高对心肌有重要保护作用     

Addition of α-Ketoglutarate to Blood Cardioplegia Improves Cardioprotection

Background. We hypothesized that myocardial content of α-ketoglutarate (α-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of α-KG could reduce metabolic abnormalities and lead to improved myocardial protection.Methods. Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of α-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured.Results. α-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 ± 2.4 μg/L versus 49 ± 4.9 μg/L (creatine kinase isoenzyme MB) and 1.1 ± 0.05 μg/L versus 2.0 ± 0.34 μg/L (troponin T). Myocardial oxygen extraction was higher during α-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the α-KG–treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion.Conclusion. Provision of α-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.(Ann Thorac Surg 1997;63:1625–34)     

Terminal Warm Blood Cardioplegia Improves Cardiac Function Through Microtubule Repolymerization

Background. To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion.

Methods. In protocol 1 isolated rat hearts were perfused at 37°C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10°C, hearts were reperfused at 37°C with one of two buffers: group C, 60-minute reperfusion with KHB (K⁺, 5.9 mmol/L; Ca²⁺, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K⁺, 15 mmol/L; Ca²⁺, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37°C with KHB containing colchicine (10⁻⁵ mol/L) for 60 minutes.

Results. There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function.

Conclusions. One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.     

常温氧合血与冷晶体心脏停搏液心肌保护对比研究

目的　为了探索较好的心肌保护方法,对持续常温氧合血心脏停搏液和间断冷晶体心脏停搏液灌注两种方法的心肌保护作用进行了对比研究。　方法　心瓣膜直视术患者３３ 例,随机分为常温氧合血心脏停搏液组（ Ｗ Ｂ Ｃ组）和冷晶体心脏停搏液组（ Ｃ Ｃ Ｃ组）。观察两组术后主要并发症、起搏器的使用情况,测定主要心肌酶。肌酸激酶、肌酸激酶同工酶、乳酸脱氢酶同工酶的释放,丙二醛、超氧化物歧化酶、三磷酸腺苷的含量以及能量储备值,观察心肌超微结构的变化。　结果　术后低心排血量综合征、室性心律失常发生例数、起搏器使用率和肌酸激酶同工酶的释放, Ｃ Ｃ Ｃ组均较 Ｗ Ｂ Ｃ组多;丙二醛释放和心内源性超氧化物歧化酶消耗, Ｗ Ｂ Ｃ组较 Ｃ Ｃ Ｃ组减少;能量保存 Ｗ Ｂ Ｃ组较 Ｃ Ｃ Ｃ组多;心肌细胞内线粒体损伤以 Ｃ Ｃ Ｃ组为重。　结论　常温氧合血心脏停搏液持续灌注在心肌保护方面较冷晶体心脏停搏液间断灌注具有明显的优越性,是一种较好的心肌保护方法。     

Effects of Calcitonin Gene-Related Peptide on Colonic Motility and Defecation in Conscious Dogs

Background

Although intra-arterial infusion of calcitonin gene-related peptide (CGRP) reportedly stimulates giant migrating contractions (GMCs) of the small intestine in conscious dogs, the effect of intravenous CGRP administration on colonic motility remains unclear. In the present study, we investigated the effects of intravenous CGRP on colonic motility and defecation and determined the underlying mechanism of action in conscious dogs.

Methods

Sixteen Beagle dogs weighing 11–13 kg were included. The effects of intravenous CGRP at doses of 3.33 (with various antagonists), 0.83, and 1.67 μg/kg on colonic motility and defecation were evaluated in neurally intact dogs (n?=?6). For comparison, dogs with transection/re-anastomosis (T/R) between the proximal and middle segments of the colon (n?=?5) and dogs with extrinsic denervation of the ileocolonic segments (n?=?5) also received intravenous CGRP at 3.33 μg/kg. All dogs were equipped with strain gauge force transducers on the ileocolon for measurement of the colonic contractile activity.

Results

Intravenous CGRP evoked GMCs and defecation in the neurally intact group; these stimulatory effects were inhibited by atropine and hexamethonium. Compared with the neurally intact group, the T/R group exhibited similar proximal colonic motility and decreased distal colonic motility after intravenous CGRP administration, whereas the extrinsic denervation group exhibited increased colonic motility overall.

Conclusions

Intravenous CGRP induces colonic motility and defecation through acetylcholine release in conscious dogs. The continuity of the enteric nerves plays an important role in CGRP-induced colonic contractions and defecation, while the extrinsic nerves suppress CGRP-induced colonic motility.

     

Normothemic Continuous Blood Cardioplegia Improves Electrophysiologic Recovery after Open Heart Surgery

Background: Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia.

Methods: Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula.

Results: Active cooling in group H on initiation of cardio-pulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168+/-32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/-26/h, compared to 3+/-5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant.     

Protective Effect of Ischemic Preconditioning on Cold Preservation and Reperfusion Injury Associated With Rat Intestinal Transplantation

OBJECTIVE: To define the protective effect of ischemic preconditioning on cold ischemia and reperfusion injury associated with intestinal transplantation, and the role of nitric oxide in this process. SUMMARY BACKGROUND DATA: Ischemia/reperfusion injury continues to be a significant obstacle in small bowel transplantation. Preconditioning is a mechanism that protects against this injury. METHODS: To study the capacity of preconditioning to prevent cold ischemia-associated injury and the inflammatory response associated with intestinal transplantation, the authors studied a control group of animals, cold ischemia groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS, and intestinal transplantation groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS. RESULTS: Histologic findings and the release of lactate dehydrogenase into the preservation solution showed that preconditioning protects against cold ischemic preservation-associated injury. Preconditioning also prevented the inflammatory response associated with intestinal transplantation, measured by the above parameters and by neutrophil recruitment in the intestine. Inhibition of nitric oxide eliminates the protective effect. CONCLUSIONS: Preconditioning protects the intestinal grafts from cold preservation and reperfusion injury in the rat intestinal transplantation model. Nitric oxide is involved in this protection.     

Machine Perfusion Preservation Improves Renal Allograft Survival

Machine perfusion (MP) has been used as the kidney preservation method in our center for over 10 years. The first, small (n = 74) prospective, single-blinded randomized study comparing MP and Cold Storage (CS) showed that the incidence of delayed graft function was higher after CS. There have been no reports in the literature on the effect of storage modality on long-term function of renal allografts. This paper presents an analysis of long-term results of renal transplantation in 415 patients operated on between 1994 and 1999. Of those, 227 kidneys were MP-stored prior to KTx. The control group consisted of 188 CS kidney transplants. Kidneys were not randomized to MP or to CS. Donor demographics, medical and biochemical data, cold ischemia time, HLA match and recipient data were collected. Standard triple-drug immunosuppression was administered to both groups. Mortality, graft survival and incidence of return to hemodialysis treatment were analyzed. Despite longer cold ischemia time and poorer donor hemodynamics in MP group, 5-year Kaplan-Meier graft survival was better in MP-stored than in CS-stored kidneys (68.2% vs. 54.2%, p = 0.02). CONCLUSION: In this nonrandomized analysis, kidney storage by MP improved graft survival and reduced the number of patients who returned to dialysis.     

Dual Exposure to Sevoflurane Improves Anesthetic Preconditioning in Intact Hearts

Background: Anesthetic preconditioning (APC) with sevoflurane reduces myocardial ischemia-reperfusion injury. The authors tested whether two brief exposures to sevoflurane would lead to a better preconditioning state than would a single longer exposure and whether dual exposure to a lower (L) concentration of sevoflurane would achieve an outcome similar to that associated with a single exposure to a higher (H) concentration.

Methods: Langendorff-prepared guinea pig hearts were exposed to 0.4 mm sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mm (H2-5; n = 8) or 0.2 mm sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.

Results: The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05).     

A Novel System Improves Preservation of Osteochondral Allografts

Background

Osteochondral allografting is an option for successful treatment of large articular cartilage defects. Use of osteochondral allografting is limited by graft availability, often because of loss of chondrocyte viability during storage.

Questions/purposes

The purpose of this study was to compare osteochondral allografts implanted in canine knees after 28 days or 60 days of storage for (1) initial (1 week) safety and feasibility; (2) integrity and positioning with time (12 weeks and 6 months); and (3) gross, cell viability, histologic, biochemical, and biomechanical characteristics at an endpoint of 6 months.

Methods

With Institutional Animal Care and Use Committee approval, adult dogs (n = 16) were implanted with 8-mm cylindrical osteochondral allografts in the lateral and medial femoral condyles of one knee. Osteochondral allografts preserved for 28 or 60 days using either the current tissue bank standard-of-care (SOC) or a novel system (The Missouri Osteochondral Allograft Preservation System, or MOPS) were used, creating four treatment groups: SOC 28-day, MOPS 28-day, SOC 60-day, and MOPS 60-day. Bacteriologic analysis of tissue culture and media were performed. Dogs were assessed by radiographs and arthroscopy at interim times and by gross, cell viability, histology, biochemistry, and biomechanical testing at the 6-month endpoint.

Results

With the numbers available, there was no difference in infection frequency during storage (5% for SOC and 3% for MOPS; p = 0.5). No infected graft was implanted and no infections occurred in vivo. MOPS grafts had greater chondrocyte viability at Day 60 (90% versus 53%; p = 0.002). For 60-day storage, MOPS grafts were as good as or better than SOC grafts with respect to all outcome measures assessed 6 months after implantation.

Conclusions

Donor chondrocyte viability is important for osteochondral allograft success. MOPS allows preservation of chondrocyte viability for up to 60 days at sufficient levels to result in successful outcomes in a canine model of large femoral condylar articular defects.

Clinical Relevance

These findings provide a promising development in osteochondral allograft technology that can benefit the quantity of grafts available for use and the quality of grafts being implanted.     

Evaluation of 7,000 Patients With Two Different Routes of Cardioplegia

Background. This study examined the efficacy and safety of retrograde cardioplegia in comparison with an antegrade/retrograde approach.

Methods. Between January 1, 1991, and December 31, 1995, 7,032 coronary artery bypass procedures, alone or in combination with valve replacement/repair, were performed using either retrograde cardioplegia (R) or an antegrade/retrograde (AR) approach. There were 4,224 patients in the R group and 2,808 in the AR group. These included elective, urgent, emergent/salvage, first operative, and redo cases.

Results. All preoperative, intraoperative, and postoperative variables listed in The Society of Thoracic Surgeons National Cardiac Surgery Database were used to compare the two groups using univariate analysis. The pump time was longer in the AR group, with fewer grafts per patient. The R group had higher predicted risk (3.2% versus 3.0%; p = 0.04), more postoperative atrial fibrillation (34% versus 31%; p = 0.006), and longer postoperative length of stay (8.8 versus 8.0 days; p < 0.001). Using The Society of Thoracic Surgeons National Cardiac Surgery Database predicted risk group model, a subgroup of 221 coronary artery bypass grafting patients in the retrograde (s-R) and 132 coronary artery bypass grafting patients in the antegrade/retrograde (s-AR) group fell into a greater incidence of predicted mortality group (≥10%). The s-R subgroup had more patients in New York Heart Association functional class IV. Univariate analysis revealed higher postoperative atrial fibrillation (51% versus 41%; p = 0.05) and longer postoperative length of stay (12.8 versus 10.8 days; p = 0.03) in the s-R subgroup versus the s-AR subgroup.

Conclusions. The results appear to favor neither approach. Preoperatively, both retrograde groups (R and s-R) had higher preoperative predicted risk, but operative mortality or complications were not significantly increased when compared with the AR and s-AR groups. Retrograde cardioplegia alone was shown to be effective in the R and s-R groups, but atrial fibrillation developed in more patients, which could have contributed to longer length of stay in these groups. Antegrade/retrograde cardioplegia offers good immediate outcome but the delivery method can be cumbersome and confusing during the adjustments of flow clamps for antegrade/retrograde delivery and may contribute to prolonged pump times. From this retrospective, nonrandomized review, it appears that retrograde cardioplegia alone provides as good myocardial protection and safety as an antegrade/retrograde approach in either the low-risk or high-risk patient.     

Isoflurane Preconditioning Improves Long-term Neurologic Outcome after Hypoxic-Ischemic Brain Injury in Neonatal Rats

Background: Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.

Methods: Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.

Results: The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection.     

肾缺血预处理对未成熟心肌的保护作用

目的探讨肾缺血预处理对未成熟心肌保护的影响，为未成熟心肌的保护提供新的方法。方法建立兔Langendorff灌注模型，将18只幼兔随机分为3组，缺血／再灌注组（I／R组）：灌注15min转为工作心15min，停灌45min，恢复灌注15min改为工作心30min；心脏缺血预处理组（CIP组）：灌注15min转为工作心15min，反复2次缺血5min再灌注5min，重复I／R组的方法；肾缺血预处理组（RIP组）：反复3次阻断左肾动脉血流5min再灌注5min，取离体心脏，灌注15min转为工作心15min，重复I／R组的方法。观察血流动力学、生化等指标。结果CIP组和RIP组的冠状动脉流量（CF）、心排血量（CO）、左心室收缩压（LVSP）恢复百分率均较I／R组升高，左心室舒张期末压（LVEDP）恢复率则较I／R组降低，差异有统计学意义（P〈0.01）；三组间比较，HR、AF恢复率差异无统计学意义（P〉0.05）；RIP组与CIP组比较各指标恢复率差异无统计学意义（P〉0．05）。RIP组与I／R组比较：心肌含水量（MWC）、血清肌酸激酶（cK）和乳酸脱氢酶（LDH）漏出率、ATP含量、丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、心肌细胞内Ca^2＋含量、心肌线粒体Ca^2＋-ATPase活性、心肌线粒体Ca^2＋含量、心肌线粒体合成ATP能力差异有统计学意义（P〈0.01），RIP组和CIP组比较各项指标差异无统计学意义（P〉0.05）。结论肾缺血预处理对未成熟心肌具有心肌保护作用。     

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n‐Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat

Heart transplantation is the therapy of choice for end‐stage heart failure. However, hemodynamic instability, which has been demonstrated in brain‐dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n‐octanoyl‐dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham‐operated (n = 9). In BDD, decreased left‐ventricular contractility (ejection fraction; maximum rate of rise of left‐ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left‐ventricular pressure; Tau), and increased end‐diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD‐treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin‐6, tumor necrosis factor TNF‐α, NF‐kappaB‐p65, and nuclear factor (NF)‐kappaB‐p105 gene expression, and increased caspase‐3, TNF‐α and NF‐kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro‐apoptotic factor caspase‐3, pro‐inflammatory cytokines, and NF‐kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion.     

缺血预处理在心瓣膜置换术中对心肌保护的作用

目的研究单一周期的缺血预处理（IP）方法在心脏瓣膜手术中对心肌的保护作用。方法2002年8月至2006年4月85例慢性心瓣膜疾病患者在我院行心脏瓣膜手术，将其随机分为两组，IP组（n=47）：主动脉阻断前文行单次缺血2min开放3min的预处理方案，阻断主动脉后采用冷晶体心脏停搏液心肌保护方法；对照组（n=38）：仅采用冷晶体心脏停搏液心肌保护方法。观察两组术前、术后心肌型肌酸激酶同工酶（CK-MB）、肌钙蛋白I（cTnI）、心电图ST-T改变、室性心律失常及ICU临床指标。结果术后两组血清CK-MB和cTnI均较术前升高；IP组术后24、48和72h的CK-MB测量值，以及术后24和48h cTnI测量值均低于对照组（P〈0．05）。IP组术后使用抗心律失常药物的比率和持续时间明显低于对照组（P〈0．05），术后使用的正性肌力药物种类和ICU停留时间少于／短于对照组（P〈0．05）。结论IP和低温高钾晶体心脏停搏液灌注方法联合使用，可以增强心脏瓣膜手术中对心肌的保护效果，降低术后心肌酶、肌钙蛋白上升水平和术后室性心律失常程度，提高手术效果。